Rotavirus genomes are distributed between 11 distinct RNA molecules, all of which must be selectively copackaged during virus assembly. This likely occurs through sequence-specific RNA interactions facilitated by the RNA chaperone NSP2. Here, we report that NSP2 autoregulates its chaperone activity through its C-terminal region (CTR) that promotes RNA-RNA interactions by limiting its helix-unwinding activity. Unexpectedly, structural proteomics data revealed that the CTR does not directly interact with RNA, while accelerating RNA release from NSP2. Cryo-electron microscopy reconstructions of an NSP2-RNA complex reveal a highly conserved acidic patch on the CTR, which is poised toward the bound RNA. Virus replication was abrogated by charge-disrupting mutations within the acidic patch but completely restored by charge-preserving mutations. Mechanistic similarities between NSP2 and the unrelated bacterial RNA chaperone Hfq suggest that accelerating RNA dissociation while promoting intermolecular RNA interactions may be a widespread strategy of RNA chaperone recycling.
- MeSH
- elektronová kryomikroskopie MeSH
- genom virový genetika MeSH
- molekulární chaperony metabolismus MeSH
- molekulární modely MeSH
- proteiny vázající RNA metabolismus MeSH
- ribonukleoproteiny metabolismus MeSH
- RNA virová genetika MeSH
- Rotavirus genetika růst a vývoj metabolismus MeSH
- sbalování RNA genetika MeSH
- virové nestrukturální proteiny metabolismus MeSH
- zabalení virového genomu genetika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH